Auxin Response Factors as a model of transcriptional control

生长素反应因子作为转录控制模型

• 批准号: 10640222
• 负责人: Lucia Strader
• 金额: $ 39.13万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10640222
• 关键词: 4-ethoxymethylene-2-phenyl-2-oxazoline-5-one; Automobile Driving; Auxins; Back; Behavior; Binding; Biochemistry; Biophysics; Charge; Chromatin Remodeling Factor; Complex; Cullin Proteins; Development; Disease; Electrostatics; Event; F Box Domain; F-Box Proteins; Face; Family; Gene Activation; Genetic; Genetic Transcription; Hormones; Knowledge; Ligands; Mediating; Mission; Modeling; Molecular; Nature; Organism; Phase Transition; Physical condensation; Plants; Point Mutation; Positioning Attribute; Process; Proteins; Reagent; Regulation; Repression; Repressor Proteins; Research; Side; Signal Transduction; Structure; System; Transcription Coactivator; Transcription Repressor; Transcriptional Regulation; United States National Institutes of Health; derepression; gene repression; insight; interdisciplinary approach; member; plant growth/development; protein degradation; protein folding; receptor; recruit; response; transcription factor; transport inhibitor; ubiquitin-protein ligase

Project Summary Hormone-mediated modulation of gene activation or repression through transcription factors is central to all organisms. AUXIN RESPONSE FACTOR (ARF) transcription factors are critical modulators of plant growth and provide an ideal model for exploring hormone control of gene activation and repression. Of the 23-member ARF family, five are considered transcriptional activators and 18 are considered transcriptional repressors, allowing for study of both of these activities in a single family. Under low auxin concentrations, Aux/IAA proteins repress ARF transcription factors via direct interaction and recruitment of chromatin remodeling factors. When auxin concentrations are high, a co-receptor complex, comprised of an F-box protein from the TRANSPORT INHIBITOR REPONSE1 (TIR1) family and an Aux/IAA repressor protein, directly binds auxin. The F-box protein participates in a Skp1-Cullin-F-box (SCF) E3 ubiquitin ligase, which targets the Aux/IAA protein for degradation. This degradation event relieves ARF transcription factor repression, allowing auxin-regulated transcription. This receptor-ligand interaction allows a very short signal transduction chain to facilitate rapid transcriptional responses to auxin. To understand the molecular underpinnings of ARF-ARF and ARF-Aux/IAA interactions, our lab solved the structure of the domain driving these interactions, finding that it folds into a Type I/II Phox and Bem1 (PB1) domain. Within this domain, there is a positively charged and a negatively charged electrostatic face on opposing sides, creating a Janus-like protein fold. This allows for front-to-back ARF oligomerization (similar to a set of bar magnets) in the packed crystal, in solution, and in the plant. In addition to the well-studied repression – derepression mechanism of regulation, our lab has discovered that activity of a subset of ARFs can be regulated by protein phase transition driven by the combination of PB1 oligomerization and an intrinsically disordered region. Phase transition of these ARFs appears to modulate responsiveness to auxin in a developmentally relevant context. We have further found that many ARFs are regulated by proteasomal degradation and have identified an E3 ubiquitin ligase involved in this process. Finally, ARF interactions can be easily manipulated using PB1 domain point mutations, allowing us to direct ARF interactions for study. Using ARFs as a model will allow us to interrogate transcription factor function in an easily manipulated system to yield broad insight into many transcription factors. We are aided in our efforts by our multidisciplinary approach, extensive auxin-related molecular toolkit, and unique reagents generated by our lab. Our lab's expertise in genetics and biochemistry/biophysics, combined with our recent discoveries of ARF condensation and proteasomal degradation, makes us well positioned to drive forward our understanding of phase transition and other mechanisms in regulation of transcription factor activity.

项目总结

项目成果

ARF19 Condensation in the Arabidopsis Stomatal Lineage.

• DOI: 10.17912/micropub.biology.000708
• 发表时间: 2023
• 期刊: microPublication biology
• 作者: Kuan, Chi;Strader, Lucia C;Morffy, Nicholas
• 通讯作者: Morffy, Nicholas

Connected phytohormone biosynthesis pathways at the core of growth-stress tradeoffs.

• DOI: 10.1016/j.molp.2022.06.005
• 发表时间: 2022-07-04
• 期刊: MOLECULAR PLANT
• 影响因子: 27.5
• 作者: Sageman-Furnas, Katelyn;Strader, Lucia
• 通讯作者: Strader, Lucia

Nucleocytoplasmic partitioning as a mechanism to regulate Arabidopsis signaling events.

• DOI: 10.1016/j.ceb.2021.01.006
• 发表时间: 2021-04
• 期刊: Current opinion in cell biology
• 影响因子: 7.5
• 作者: Allen JR;Strader LC
• 通讯作者: Strader LC

Defying Gravity: WEEP promotes negative gravitropism in Prunus persica (peach) shoots and roots by establishing asymmetric auxin gradients.

对抗重力：WEEP 通过建立不对称的生长素梯度来促进桃（桃）芽和根的负向地性。

• DOI: 10.1101/2023.05.26.542472
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Kohler,AndreaR;Scheil,Andrew;HillJr,JosephL;Allen,JeffreyR;Al-Haddad,JameelM;Goeckeritz,CharityZ;Strader,LuciaC;Telewski,FrankW;Hollender,CourtneyA
• 通讯作者: Hollender,CourtneyA

Emerging Roles for Phase Separation in Plants.

• DOI: 10.1016/j.devcel.2020.09.010
• 发表时间: 2020-10-12
• 期刊: Developmental cell
• 影响因子: 11.8
• 作者: Emenecker RJ;Holehouse AS;Strader LC
• 通讯作者: Strader LC